Human blood peripheral monocyte/macrophages release in culture a mononuclear cell factor (MCF) which stimulates the production of collagenase and prostaglandin E2 by human rheumatoid synovial cells and dermal fibroblasts. These two products play a role in connective tissue destruction. MCF has an apparent molecular weight of approximately 15 000 and is biologically and biochemically indistinguishable from interleukin 1. MCF therefore belongs to the well-documented nonimmune biological activities attributed to interleukin 1. Studies on the mechanisms of production and action of such monokine(s) have been difficult in view of the minute quantities produced by freshly isolated cells or from human monocytic lines. Starting from lectin-stimulated human blood mononuclear cells, we have isolated poly(A)+ RNA and studied its translation following microinjection into Xenopus laevis oocytes. The mRNA translation products stimulated collagenase and prostaglandin E2 production in human rheumatoid synovial cells and dermal fibroblasts. The size of MCF-mRNA was estimated to be 10 S. The mRNA of a member of the interleukin 1 family can now be studied in a system based on a specific and direct relevant biological assay and eventually compared with those of other monokines.

Synthetic calcium pyrophosphate dihydrate crystals and, to a lesser extent, synthetic hydroxyapatite crystals increased the amount of interleukin-l/mononuclear cell factor released by human blood monocytes, as measured by collagenase and prostaglandin Ez production by rabbit chondrocytes, human dermal fibroblasts, and adherent rheumatoid synovial cells. The same crystals also directly induced collagenase and prostaglandin Ez secretion by rabbit chondrocytes, and potentiated the action of interleukin-llmononuclear cell factor on chondrocytes. These mechanisms may be important in the pathogenesis of the destructive arthropathies associated with these crystals.The processes that lead to irreversible articular cartilage destruction in inflammatory and degenerative